Management of radiation induced proctitis

Definition

Radiation proctitis is a term used to describe radiation-induced injury to the rectum following radiation therapy to the pelvic area.^r Depending on the time of onset, and to a lesser extent the clinical features and histology, radiation proctitis is defined as being either acute or chronic.

Pathophysiology

The rectum is at risk of injury during pelvic irradiation because of its fixed position and close proximity to target organs.^r

Acute radiation proctitis is caused by direct radiation injury to the rectal mucosa, which results in inflammation with oedema, ulceration and shedding of the mucosa.^r

Chronic radiation proctitis is related to late effects of radiation damage. Injury to small blood vessels causes progressive ischaemic changes and atrophy of the rectal mucosa. This is followed by ulceration, fibrosis and telangectasia development. In severe cases, strictures and fistulae may result.

Incidence/prevalence

Exact figures vary, but it is widely accepted that the majority of patients receiving pelvic irradiation will develop some degree of acute radiation proctitis.

The incidence of chronic radiation proctitis is less clear. Rates cited in reviews typically range between 2% to 30%.^rrrrrrrr However, it has been suggested that a much higher percentage of patients receiving pelvic radiation will have a permanent change to their bowel habits and for a significant number this may impair their quality of life.^r The condition is probably underreported, as patients may be reluctant to report symptoms due to embarrassment or a belief that nothing can be done about them.^rrr

Furthermore, it is unclear whether the incidence of radiation proctitis is increasing or decreasing. Although newer radiation therapy techniques may reduce the damage to surrounding tissues, potentially reducing the incidence of proctitis,^r it is possible that the higher doses used may have the opposite effect.^r Also, as the number of cancer patients receiving radiation to the pelvic area increases, the incidence of radiation proctitis may also increase.^r

Onset/duration

Acute radiation proctitis presents during or shortly after radiation therapy. It lasts for less than 6 months after treatment and in most cases resolves within a few weeks of finishing therapy.

Chronic radiation proctitis may follow on from acute radiation proctitis or occur after a symptom-free period (generally more than 90 days after completion of treatment).^rrr The median time of presentation is around 8-12 months after treatment but can also present many years after radiation therapy.^r There have been reports of spontaneous improvement or resolution of symptoms in some patients over time however large-scale studies are required to confirm this.^rrr

Risk factors

Radiation proctitis occurs most commonly in patients receiving treatment for prostate, cervical and rectal cancers but can also occur after radiation therapy to the pelvic area for other tumour types.^r Radiation therapy-related factors affecting the risk of rectal injury include the:

• volume of rectum irradiated
• dose received
• method of delivery*

*In the case of delivery method, the relative risks and benefits of different modalities are yet to be determined. The volume of rectum exposed to radiation during traditional field based external beam radiation therapy is greater than that likely to be affected during brachytherapy, 3-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). However, the higher prescribed doses used with these treatments mean that adjacent tissues may still receive significant radiation dose. While there is some evidence that IMRT may be associated with reduced levels of rectal damage, further studies are required before any definitive recommendations can be made.^r

Other proposed risk factors are patient related but the extent to which they influence the occurrence of radiation proctitis is unclear.^r

Factors include:^rrrrr

• tumour stage
• genotypic susceptibility to radiation toxicity
• patient’s general condition e.g. age, malnutrition
• previous abdominal surgery
• smoking
• concurrent treatments, particularly chemotherapy
• co-morbidities, including diabetes, vascular disease, inflammatory bowel disease and HIV.

There is also evidence that the occurrence and/or severity of acute radiation proctitis may be predictive of the development of chronic radiation proctitis.^rrr This may have implications for possible future preventative strategies and interventions.^r

Symptoms

Radiation proctitis results in a range of bowel symptoms which can significantly impair patient quality of life. Since the bowel has a limited range of responses to injury, there is an overlap between the symptoms experienced by patients with the different forms of radiation proctitis.^r

In acute radiation proctitis, the most common symptom is non-bloody diarrhoea. However, among patients with chronic rectal proctitis there is more variation in symptoms. In particular, bleeding is the predominant feature in a subset of patients, while others have greater problems with urgency. This has led to the suggestion that there may be multiple syndromes underlying the collection of symptoms usually accepted as indicating proctitis.^r

Symptoms of acute radiation proctitis include:

• diarrhoea (common)
• faecal urgency
• tenesmus (the feeling of needing to pass stools even when the bowel is empty)
• mucous discharge
• abdominal pain
• bleeding (uncommon).

Symptoms of chronic radiation proctitis include:

• diarrhoea
• constipation
• faecal urgency
• faecal incontinence
• tenesmus (the feeling of needing to pass stools even when the bowel is empty)
• anorectal dysfunction
• mucous discharge
• rectal bleeding (common) – can result in anaemia symptoms resulting from intestinal obstruction or fistulae.

Investigations and diagnosis

Acute radiation proctitis is diagnosed on the basis of symptoms and specific investigations are not generally required.^r

Chronic radiation proctitis may need to be investigated more extensively. The key requirements are to exclude other possible causes of the patient’s symptoms and to identify what management strategies may be of benefit.

It is important to remember that not all gastrointestinal symptoms reported by patients who have had pelvic irradiation are necessarily radiation related.^r In addition, even when radiation-induced rectal injury exists, more proximal gastrointestinal injury may also affect bowel function and contribute to patient symptoms.^r Referral to a gastroenterologist for comprehensive assessment may be appropriate in some cases.^r

Patient assessment may include:^rrrrr

• detailed history
• blood tests if indicated, e.g., haematological and biochemical profiles, inflammatory and tumour markers
• stool samples to exclude infectious causes
• proctoscopy or sigmoidoscopy (possibly with biopsy)*
• imaging if indicated (not routinely used), e.g. MRI, CT, Ba enema.

* Endoscopy can be useful to confirm the diagnosis and exclude other possible causes. However, it is recommended that biopsy is used with caution because of the risk of fistula development.^r

Grading

There is not a single universally accepted grading system for radiation proctitis.^rr

The National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) is probably the most widely-used measure, although this is not specific to radiation-induced injury. It provides grading for proctitis, as well as for individual symptoms including diarrhoea, rectal haemorrhage and faecal incontinence as seen in Table 1.^r

Common Terminology Criteria for Adverse Events (CTCAE) v5.0, 27 November, 2017

The European Organisation for the Research and Treatment of Cancer (EORTC) and the US-based Radiation Therapy Oncology Group (RTOG) have produced a grading system for the assessment of acute and late radiation-induced gastrointestinal morbidity, although this is not limited to proctitis. The impact on patient quality of life is also an important aspect of radiation proctitis. An EORTC questionnaire is currently under review for the measurement of quality of life in patients with radiation proctitis following pelvic irradiation.^r A rectal bleeding quality of life scale (RBQOLS) is also available for patients where this is a major symptom.^r

Prevention

The primary approach to the prevention of radiation proctitis is the use of contemporary conformal radiation therapy techniques (e.g. intensity-modulated radiation therapy, image-guided radiation therapy) that minimise the dose of radiation to the rectum while maximising the dose to the tumour.

Attempts to use adjunctive medical therapy (e.g. amifostine) to prevent the development of radiation proctitis has shown some benefit in small trials in reducing symptoms of both acute and chronic radiation proctitis.^rr Rectal administration has also been trialed^r and it is recommended by MASCC/ISOO for the prevention of radiation proctitis,^r although it is not widely used in clinical practice.

Sucralfate has also been evaluated for prophylaxis against acute radiation injury.^r However, placebo-controlled phase III trials have detected no benefit from either topical or oral sucralfate.^rr

Physical techniques

As well as the newer radiation delivery methods, other physical techniques have been used to minimise the dose of radiation reaching normal tissues. For example, attempts to protect the rectum during radiation therapy for prostate cancer have included placing the patient in a supine position, transperineal injection of collagen between the prostate and rectum, and prostate immobilisation using endorectal balloons.^r

Dietary interventions

A number of dietary interventions have been trialled in patients receiving pelvic irradiation in an attempt to either prevent or control gastrointestinal symptoms. Such symptoms may result from radiation proctitis but also from more proximal bowel damage. Interventions have included lactose restriction, fat restriction or modification and fibre supplementation. Although no specific treatments have been recommended, there is some evidence that dietary modification may reduce acute symptoms of diarrhoea in patients receiving pelvic irradiation.^r

Treatment

In the absence of comprehensive management guidelines, a range of treatment options have been explored. These are aimed at minimising the risk of injury to the rectum during radiation therapy, providing supportive treatment for patients with acute radiation proctitis, and symptom-based management of those with chronic radiation proctitis.

Treatment of established radiation proctitis is generally classified as being medical, endoscopic or surgical, but the evidence for many therapies is limited and more large-scale, prospective trials are required to evaluate their benefit.^r

Medical treatments

A range of medical treatments have been used to manage radiation proctitis. Some of these are supportive measures and include rehydration therapy, stool softeners, antispasmodics and oral and topical analgesics.

Although there are no definitive guidelines currently available for the management of radiation proctitis, a number of recommendations are included in clinical practice guidelines developed by The Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO).^r Several other therapies have been evaluated in patients with radiation proctitis, including sodium butyrate, metronidazole, formalin however there is limited evidence to support their use.^r The use of a structured clinical algorithm with targeted management may also improve radiation therapy-induced gastrointestinal symptoms.^r Many authors point out that large, prospective, randomised, controlled trials are needed to critically evaluate the available options.^rrr 

Endoscopic treatments

Endoscopic treatments: There are a variety of endoscopic approaches which may assist in the management of chronic radiation proctitis designed to control bleeding. The most common of these is Argon plasma coagulation (APC) due to cost effectiveness, positive results and the ability to treat large areas.

Surgery

Surgery may be considered for patients with chronic radiation proctitis where conservative treatments have been unsuccessful.

Patients should be referred to a gastrointestinal specialist to explore options where appropriate in conjunction with the treating radiation oncologist.

Treatment strategy

Acute proctitis

Patients with severe symptoms of acute radiation proctitis may need to have their radiation therapy suspended for a short period.^r Otherwise, treatment is of a supportive nature including:

• maintaining adequate hydration
• dietary changes (see above)
• antidiarrhoeals as required
• analgesics if pain is a problem
• antispasmodics for tenesmus
• topical analgesia for anal soreness
• oral/rectal steroids and/or butyrate enemas may be considered.

Chronic proctitis

Chronic radiation proctitis can present with a range of symptoms and these will largely determine the choice of management strategy. The level of intervention required will depend on the severity of symptoms and the risk-benefit profile of available treatment options.

Because of uncertainty about the natural history of chronic radiation proctitis, the limited evidence for many therapies and the risk of adverse effects, a conservative management approach is advocated by some authors.^rrr This would include supportive measures similar to those used in acute proctitis. In addition, patients with rectal bleeding who are taking aspirin or warfarin should have their need for these medications reviewed.^r Consideration should also be given to other factors which may be contributing to symptoms including more proximal gastrointestinal damage producing gastrointestinal hurry.^r Additional treatments would be considered on the basis of the evidence available for their use and the likely risk of adverse effects, as outlined above.

Discuss with the patient prior to treatment the risk of developing radiation proctitis.^r Those that develop proctitis should be advised of the likely success rates and possible complications of the treatment options on offer.

Ensure the patient is aware to immediately report any changes in bowel habit during and after treatment.

Educate the patient regarding self-care strategies including:

• dietary changes which may assist in the management of symptoms
• the appropriate use of analgesics, anti-diarrhoeals and antispasmodics

Provide the patient with information about the management options for radiation proctitis as appropriate.

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